Submissions for variant NM_000051.4(ATM):c.2098C>T (p.Gln700Ter)

dbSNP: rs786202743

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165710	SCV000216451	pathogenic	Hereditary cancer-predisposing syndrome	2023-01-06	criteria provided, single submitter	clinical testing	The p.Q700* pathogenic mutation (also known as c.2098C>T), located in coding exon 12 of the ATM gene, results from a C to T substitution at nucleotide position 2098. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000165710	SCV000266014	likely pathogenic	Hereditary cancer-predisposing syndrome	2015-11-20	criteria provided, single submitter	clinical testing
GeneDx	RCV000430405	SCV000516075	pathogenic	not provided	2018-02-28	criteria provided, single submitter	clinical testing	This pathogenic variant is denoted ATM c.2098C>T at the cDNA level and p.Gln700Ter (Q700X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in one individual with ataxia-telangiectasia (Hoche 2014), as well as in at least three individuals with breast cancer (Shirts 2016, Bubien 2017). We consider this variant to be pathogenic.
Invitae	RCV000525812	SCV000622305	pathogenic	Ataxia-telangiectasia syndrome	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln700*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 186167). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000762816	SCV000893174	pathogenic	Familial cancer of breast; Ataxia-telangiectasia syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165710	SCV001733907	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-19	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 13 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with ataxia telangiectasia in the compound heterozygous state (PMID: 25037873) and at least three individuals with breast cancer (PMID: 26845104, 28691344). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Baylor Genetics	RCV003462186	SCV004207747	pathogenic	Familial cancer of breast	2023-08-18	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003462186	SCV004932047	pathogenic	Familial cancer of breast	2024-01-17	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.